Fundamentally important to the future of pulmonary medicine is a better description and understanding of the human lung and its response to disease, injury, and treatment - based not upon global measures but upon quantifiable regional features. Currently, x-ray-based multidimensional-row computed tomography (MDCT) is the imaging modality of choice for the comprehensive evaluation of the lung, due in large part to the significant advances made in both temporal and spatial resolution and the quantifiable nature of the modality. We have developed and validated tools for MDCT lung image segmentation, registration (across changing lung volumes and between subjects), 2D &3D textural analysis, high-resolution ventilation and perfusion measurement, and applied these techniques in animal models and human subjects to establish an atlas/model of the normal lung against which early pathology can be detected. However, at the same time, the increasing propensity of public policy to mandate limits on the use of ionizing radiation threatens to limit full deployment of these emerging quantitative MDCT tools. Fortunately, through new technological methods significant dose reduction is possible. The refinement and evaluation of these low dose methods, constitute a major focus of this renewal to maximize translation into the clinics. Hyperpolarized gas-based methods have recently brought attention to the role that magnetic resonance imaging (MRI) can play in studying the proton, poor lung. Quantitative tools which express physiologically important parameters in a reliable and repeatable manner are critical for both modalities, and to take advantage of clear synergies. Our MDCT methods will provide the needed gold standards to facilitate evaluation of MRI as a complimentary tool for assessing the lung. This likely will bring needed paradigm shift in the process by which we discover and evaluate new therapeutic modalities to treat clinical and pre-clinical stages of lung disease, and to prevent the progression to debilitating end stage scenarios. In this renewal, we focus on 5 specific aims: 1: Establish quantitative measures of lung structure and function via use of low dose CT scans;2: Quantitatively evaluate and validate MR-based imaging methods and incorporate into the armamentarium for comprehensive functional and structural evaluation of the lung;3: Determine the role of gas density (Xe vs He vs room air) on regional measures of lung function;4: Continue development and validation of atlases of normal human and sheep lungs. Construct and evaluate population-specific atlases (smokers,COPD, experimental emphysema) to detect deviations from normal;5: Maintain these atlases/models in the public domain through our open source MIFAR project.